NCT06519682

A Pilot Study Investigating Upfront Adaptive Immunotherapy Approach in Children, Adolescent and Young Adult (CAYA) Patients With Replication-Repair Deficient (RRD) High-Grade Gliomas (HGG)

U-R-Immune Glioma (CA209-1245): A Pilot Study Investigating Upfront Adaptive Immunotherapy Approach in Children, Adolescent and Young Adult (CAYA) Patients With Replication-Repair Deficient (RRD) High-Grade Gliomas (HGG)

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Daniel Morgenstern · Academic / Other
• Sex: All
• Age: 12 Months – 25 Years
• Healthy volunteers: Not accepted

Summary

This is open label, multicentre, single arm, pilot study of upfront nivolumab in patients with RRD-glioblastoma with favorable immune/genomic biomarkers. The purpose of the study is to use upfront immune checkpoint inhibitor (ICI) to delay/avoid radiation for patients with RRD-glioblastoma with favorable clinical (Gross total resection (GTR) or near total resection (NTR)) and biological (RRD, hypermutation, immune activation) biomarkers. At progression, patients will be undergoing surgery/biopsy and will get a combination of radiation + ICI followed by maintenance ICI. This model will allow us to additionally study the evolution tumor in response to ICI. The study will have two domains.

Detailed description

Domain 1 - Upfront ICI Initially 12 eligible patients will be enrolled for upfront ICI. At 12 weeks assessment if \>6 patients have response (NO radiation for progression/recurrence), an additional 6 patients will be enrolled for upfront ICI. Nivolumab will be administered at a dose of 6 mg/kg every 4 weeks (cycle). All patients will be assessed at 12 weeks (3 cycles) from the start of ICI. If 6 or more out of 12 RRD-glioblastoma will recur/progress, no more patients will be recruited to this domain. Domain 2 - Radiation + ICI → maintenance ICI All the patients experiencing tumor progression on domain 1 will be eligible for domain 2 and will receive a combination of radiation and nivolumab followed by maintenance nivolumab for a total of 2 years (24 cycles). To be eligible for domain 2 post recurrence patients will need surgery/biopsy at recurrence. If 6 RRD-glioblastoma will recur/progress at 12 weeks on domain 1 then 8 additional eligible patients may be enrolled directly in domain 2. Patients may receive up to a total of approximately 2 years of treatment (up to 24 cycles). Follow-up may continue for up to one year following treatment discontinuation.

Conditions

• High Grade Glioma
• Replication Repair Deficient

Interventions

Type	Name	Description
DRUG	Nivolumab	All patients will be administered Nivolumab with or without radiation
RADIATION	Radiation	Radiation

Timeline

• Start date: 2024-12-06
• Primary completion: 2026-12-01
• Completion: 2029-08-01
• First posted: 2024-07-25
• Last updated: 2025-08-29

Locations

1 site across 1 country: Canada